PKC zeta controls DNA topoisomerase-dependent human caspase-2 pre-mRNA splicing

FEBS Lett. 2008 Jan 23;582(2):372-8. doi: 10.1016/j.febslet.2007.12.032. Epub 2007 Dec 31.

Abstract

Caspase-2 exists as two main isoforms: the caspase-2L long isoform, which is pro-apoptotic, and the caspase-2S short isoform, which may be anti-apoptotic. Topoisomerase inhibitors drive inclusion of exon 9, specific for Casp-2S mRNA, and lower Casp-2L [corrected] mRNA and protein. With cell lines engineered to express various PKC isoforms, we demonstrate that PKC zeta, but not PKCalpha, positively regulates Casp-2S mRNA assembly triggered by topoisomerase inhibitors. In addition, exon 9 inclusion is lowered in mitosis but increased in the G1/S phase. Hence, the control of caspase-2 exon 9 inclusion by topoisomerase inhibitors depends on phosphorylation and/or dephosphorylation events, and on the cell cycle phase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Caspase 2 / metabolism*
  • DNA Topoisomerases / metabolism*
  • Humans
  • Protein Kinase C / metabolism*
  • RNA Precursors / metabolism*
  • RNA, Messenger / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • U937 Cells

Substances

  • RNA Precursors
  • RNA, Messenger
  • protein kinase C zeta
  • Protein Kinase C
  • Caspase 2
  • DNA Topoisomerases